During 1974 we are planning to do the following: 1. To finish the work (which is currently in progress) on stimulated and unstimulated DNA synthesis of human lymphocytes in the presence and absence of isoniazid. This also includes karyotype analysis of metaphase chromosomes containing incorporated H3-TdR during the unstimulated DNA synthesis in tissue cultures. 2. To continue the work on the binding of tritiated poly-L-lysine to human metaphase chromosomes isolated from tissue cultures containing isoniazid, imipramine and Li Cl. This study will be similar to the one described for CPZ in this report. The morphology of metaphase chromosomes will be studied with regard to dose and time of exposure to the above mentioned drugs. 3. To finish the experiments concerned with the effect of L-DOPA and of haloperidol on Rhesus monkey lymphocytes. In these experiments the drugs were administered to the animals and not to tissue cultures of lymphocytes. There are three aspects to this study, namely: stimulated DNA synthesis, unstimulated DNA synthesis and karyotype analysis of H3-TdR-labeled metaphase chromosomes. 4. To continue studies on the ability of metaphase chromosomes isolated either from drug-treated or from control cultures to serve as templates in RNA polymerase reaction. Preliminary experiments indicated that one can detect by autoradiography newly synthesized radioactive RNA chains attached to specific segments of metaphase chromosomes. 5. To continue the work on the effect of CPZ and imipramine on the secondary and tertiary structure of DNA. These studies are in progress and involve such methods as equilibrium dialysis, ultracentrifugation, measurement of intrinsic viscosities and thermal denaturation and renaturation of DNA.